...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of interferon and cytokine research: The official journal of the International Society for Interferon and Cytokine Research >Creation of Interferon-a8 Mutants with Amino AcidSubstitutions Against Interferon-a Receptor-2 BindingSites Using Phage Display System and Evaluationof Their Biologic Properties
【24h】

Creation of Interferon-a8 Mutants with Amino AcidSubstitutions Against Interferon-a Receptor-2 BindingSites Using Phage Display System and Evaluationof Their Biologic Properties

机译：使用噬菌体展示系统创建具有氨基酸取代干扰素-α2受体结合位点的干扰素-a8突变体并评估其生物学特性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

In this study, we describe the creation of three interferon-alpha (IFN-alpha)8 mutants with markedly higher antiviral and antiproliferative activities in comparison with those of the wild-type (wt)IFN-a8, wtIFN-a2, and IFN-conl using a phage display system. Sequence analysis showed that three out of the six hot-spot amino acid residues of wtIFN-a8 known to be important for the interaction with the IFN-alpha receptor-2 (IFNAR-2)-binding sites were substituted to other amino acids and the others remained. Although affinity analysis revealed that the dissociation constant (K_D) of IFN-a8 mutants was almost the same with that of wtIFN-a8, furthermore, the rates of association (k_a) and dissociation (k_d) were relatively lower. These results suggest that changes in the surface electronic charge of amino acid residues lead to changes in binding affinity and kinetics (prolonged dissociation time) toward the IFNAR-2, resulting in the modification of the biological activity. Moreover, our results demonstrate that the molecular engineering of the IFN-a8 provides important insight into action of IFN and also it would be useful in the development of therapeutically prominent IFN preparations than those used in clinical practice.
机译：在这项研究中，我们描述了与野生型（wt）IFN-a8，wtIFN-a2和IFN-α相比，具有明显更高的抗病毒和抗增殖活性的三个干扰素-α（IFN-α）8突变体的创建使用噬菌体展示系统进行控制。序列分析表明，wtIFN-a8的六个热点氨基酸残基中的三个对与IFN-αreceptor-2（IFNAR-2）结合位点的相互作用很重要，被其他氨基酸取代，并且其他人仍然存在。尽管亲和力分析显示IFN-a8突变体的解离常数（K_D）与wtIFN-a8几乎相同，但缔合率（k_a）和解离率（k_d）相对较低。这些结果表明，氨基酸残基的表面电子电荷的变化导致对IFNAR-2的结合亲和力和动力学（延长的解离时间）的变化，从而导致生物学活性的改变。而且，我们的结果表明，IFN-α8的分子工程学提供了对IFN作用的重要见解，并且比起临床实践中的研究，它在开发治疗上显着的IFN制剂中将是有用的。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号